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Targeting NF-κB Signaling with Natural Products: A Promising Therapeutic Strategy for Cardiovascular Diseases
Rui Liu1,2, Wencong Liu1,2, Ling Dong1,2
1College of Food and Pharmaceutical Engineering, Wuzhou University, Wuzhou 543002, China.
Biomolecules
|May 4, 2026
Summary
Natural products show promise in treating cardiovascular diseases (CVDs) by targeting the nuclear factor kappa B (NF-κB) pathway. This review analyzes their mechanisms and clinical potential, addressing challenges for therapeutic development.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Natural Product Chemistry
Background:
- Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide, driven by inflammation, oxidative stress, and vascular remodeling.
- The nuclear factor kappa B (NF-κB) signaling pathway is a critical regulator in CVD progression, promoting inflammation and endothelial dysfunction.
- Natural products offer a promising therapeutic avenue due to their diverse structures, multi-targeted actions, and low toxicity.
Purpose of the Study:
- To review and critically analyze the use of natural products in treating CVDs via the NF-κB pathway.
- To detail the molecular mechanisms and effects of natural products on various CVD models.
- To discuss the challenges and potential solutions for translating natural product therapies into clinical practice.
Main Methods:
- Systematic review of in vitro, in vivo animal, and human clinical studies on natural products targeting the NF-κB pathway in CVDs.
- Analysis of molecular mechanisms, including inhibition of NF-κB p65 nuclear translocation and modulation of upstream/downstream signaling pathways.
- Evaluation of evidence strength for natural products in specific CVD indications like atherosclerosis and myocardial ischemia/reperfusion injury.
Main Results:
- Natural products, including flavonoids, terpenoids, and polyphenols, effectively modulate the NF-κB pathway to reduce inflammation and oxidative stress.
- Demonstrated efficacy in preclinical models of atherosclerosis, hypertension, myocardial ischemia/reperfusion injury, and pulmonary arterial hypertension.
- Identified key molecular targets and pathways influenced by natural products, such as TLR4/MyD88, PI3K/Akt, MAPK, Nrf2/HO-1, and SIRT1.
Conclusions:
- Natural products represent a viable strategy for CVD prevention and treatment by targeting the NF-κB pathway.
- Overcoming translational challenges like poor bioavailability and incomplete mechanistic understanding is crucial for clinical application.
- Further large-scale clinical trials are needed to validate the therapeutic potential of natural products for cardiovascular diseases.
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